See the publication here: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(26)00155-2/fulltext

And read about the findings here….

or…

New Publication alert (and this one has got some immunologic hidden gems)!”Assessing SARS-CoV-2 immune markers in vaccinated asymptomatic adults after household exposure in Canada (AB-PROTECT): a prospective cohort study” By Drs J. Breznik (@uofguelph.bsky.social), and C Kandel (@mghtoronto.bsky.social) & team @lancetmicrobe.bsky.social 1/n

Let’s start with study design. Someone tests positive for COVID so we get blood as quick as we can from all the adults who live with them. Everyone in that household is going to be exposed so we want to figure out which immune responses protect those who don’t get sick versus those who do. 2/n

Everyone in the study has been vaccinated so they’ve all got antibodies and some T cells against the Spike protein. Some folks have some T cells that seem to be reactive against related coronaviruses or possibly a previous COVID infection. Our goal – figure out which of these protects people and which are just immunologic noise. 3/n

First stop antibodies – are people who make more antibodies or who make ‘stickier’ antibodies (i.e. ‘neutralizing’ antibodies) more protected from infection? No (although folks who didn’t wear masks or isolate their sick housemate got an antibody boost after exposure). (Neither serum IgG or IgA for the immunology aficionados) 4/n

Next stop -T cells and here’s where things get interesting. People who got sick have fewer CD8+ T cells (the ones that specialize in killing virus infected cells) against the Omicron variant, but here’s the part I’m especially excited about. T cells make cytokines which kick other immune cells into action.. 5/n

…to measure how well a T cell does it’s job, immunologists usually measure the cytokines it makes – IL2, TNF, IFNg. Other groups have seen if anti-COVID T cells making these cytokines are the secret to protection and found that they are not. So did we BUT (read on for the grand reveal)…6/n

…we looked at one less studied cytokine – GMCSF – which T cells make to kick innate immune cells like macrophages into gear during an infection. Guess what seems to be the secret to not getting COVID symptoms? Having anti-COVID T cells that make GMCSF! 7/n

Backstory – this finding has been a long-time in the making and chatting with the team we are a bit hazy on whose idea it was to check GMCSF and why we included it when the dozens upon dozens of similar studies did not. Other groups have found hints that kicking innate immunity into gear might help so we thought ‘worth a shot’ and it was! 8/n

Take home message – we may have found a new correlate of protection against COVID but we still don’t know why some people’s anti-COVID T cells make GMCSF and others don’t. As exciting as this is, there are some caveats to our study…9/n

The folks included are young(ish), healthy(ish) and this was mostly during the first Omicron wave. Whether this applies to all COVID infections and all waves remains to be seen…10/n

…as one of the 8 (8!) reviewers pointed out, we only got blood from folks after someone in their house was sick and it usually takes 2-3 days for a person to develop symptoms so their housemates may well have been in the early stages of illness before we got their blood….11/n

….because it takes about 5-10 days to make and detect a brand new GMCSF producing T cell, our interpretation was that these cells were preexisting (i.e generated from previous vaccinations or infections), but we can’t rule out that people who could fight infections were making these really quickly 12/n

….if you’ve read this far you love immunology so check out the other neat observations (people who got sick had more anti-Spike Th17 cells and T cell polyfunctionality was not associated with protection – cool, eh?). 13/n

Thanks to the whole team – it was a tremendous amount of work from the logistics of blood delivery from homes in TO to my lab in #HamOnt, to the extensive antibody responses from @gingraslab.bsky.social, Chris Verschoor’s most exceptional T cell analysis…14/n

…. the team @mcmasteruniversity.bsky.social ‘s Human Immune Testing Suite (esp Ying Wu) and of course Dr @jabreznik.bsky.social ‘s late nights doing T cell assays & Dr Kandel & McGreer’s leadership. Thanks to all involved! 15/15 https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(26)00155-2/fulltext